Everolimus for advanced pancreatic neuroendocrine tumours: a subgroup analysis evaluating Japanese patients in the RADIANT-3 trial

Jpn J Clin Oncol. 2012 Oct;42(10):903-11. doi: 10.1093/jjco/hys123. Epub 2012 Jul 31.

Abstract

Objective: Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study.

Methods: Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions.

Results: Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31-not available) with everolimus vs 2.83 months (95% confidence interval, 2.46-8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08-0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%).

Conclusions: These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials, Phase III as Topic
  • Double-Blind Method
  • Everolimus
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Neuroendocrine Tumors / drug therapy*
  • Neuroendocrine Tumors / mortality
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / mortality
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survival Rate
  • Young Adult

Substances

  • Immunosuppressive Agents
  • Everolimus
  • Sirolimus